Positive and negative controls on cell growth.
Positive and negative controls on cell growth.
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细胞生长的阳性和阴性对照。
DOI：
10.1021/bi00447a001
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发表时间：
1989
期刊：
影响因子：
2.9
通讯作者：
Weinberg,RA
中科院分区：
文献类型：
--
作者：
Weinberg,RA
怀特黑德生物医学研究所，九剑桥中心，剑桥，马萨诸塞州02142，和生物系，麻省理工学院，剑桥，马萨诸塞州02139癌基因在过去十年中引起了极大的关注，似乎为我们提供了癌症起源的分子水平上的许多解释。我们现在计算出多达50种不同的细胞癌基因，其中许多能够诱导至少一些与肿瘤状态相关的细胞表型。其中，大约有12种与人类癌症的病因有直接关系。其余的已被发现与多种哺乳动物和禽类逆转录病毒有关，已被这些转导病毒从细胞基因组中提取出来。然而，在这个庞大的群体中，由于与先前已知的致癌基因的核酸同源性，已经发现了其他人（Bishop, 1983; Varmus, 1984）。综上所述，这些基因留下了一个丰富复杂的细胞生长调控回路的印象，这个回路可以在许多点上被致癌基因及其编码蛋白的作用所干扰。尽管这种复杂性已被充分证明，但仍有理由相信致癌基因最多只能部分解释癌症的分子和遗传机制。这些原因源于所有这些基因共有的两个属性。首先，癌基因以这样或那样的方式作用于细胞生长。因此，癌基因范式忽略了可能存在的一个同样复杂和重要的细胞生长调节网络，该网络致力于抑制或限制细胞生长。这种负调控基因，就其存在的程度而言，当它们丢失或失活时，可能与癌症有关；这种缺失会消除细胞生长的正常刹车或限制，从而引发肿瘤的失控生长。其次，癌基因总是作为靶细胞基因组的显著改变的结果而出现。因此，在人类肿瘤中，研究的细胞癌基因被发现是由于正常的明确的体细胞突变而产生的。这里描述的一些工作得到了国家癌症研究所杰出研究者资助5-R35-CA39826和美国癌症协会资助CD355给RAW，他是美国癌症研究教授。
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Cambridge, Massachusetts 02142, and Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Received May 15, 1989; Revised Manuscript Received June 12, 1989 e oncogenes that have attracted great attention over the past decade would seem to provide us with much of the ex-planation at the molecular level of the origins of cancer. We now count as many as 50 distinct cellular oncogenes, many of which are able to induce at least some of the cell phenotypes associated with the neoplastic state. Of these, about a dozen are directly implicated in the etiology of human cancer. The remainder have been found associated with a variety of mammalian and avian retroviruses, having been abstracted from the cellular genome by these transducing viruses. Yet others in this large group have been uncovered by virtue of nucleic acid homologies with previously known oncogenes (Bishop, 1983; Varmus, 1984). Taken together, these genes leave an impression of a richly complex cellular growth reg-ulatory circuitry that can be perturbed at many points by the actions of oncogenes and their encoded proteins. In spite of this already well-documented complexity, there are reasons to believe that oncogenes can provide at best only part of the explanation of the molecular and genetic mechanisms of cancer. These reasons stem from two attributes that are shared by all these genes. First, oncogenes actin one way or another as positive effectors of cell growth. As such, the oncogene paradigm overlooks the possible existence of an equally complex and important cellular growth regulatory network that is dedicated to suppressing or constraining cell growth. Such negative regulatory genes, to the extent that they exist, could become involved in cancer when they are lost or inactivated; such loss would remove a normally existing brake or constraint on the cell’s growth, thereby triggering the runaway growth of neoplasia. Second, oncogenes invariably arise as consequences of so-matic alterations of the target cell genome. Thus, in human tumors, the cellular oncogenes studied have been found to arise as a consequence of well-defined somatic mutations of normal tSome of the work described here was supported by Outstanding Investigator Grant 5-R35-CA39826 of the National Cancer Institute and by American Cancer Society Grant CD355 to RAW, who is an Am-erican Cancer Research Professor.